Xenobiotic phenols in early pregnancy amniotic fluid

Engel, Stephanie M.; Levy, Brynn; Liu, Zhisong; Kaplan, Dana; Wolff, Mary S.

doi:10.1016/j.reprotox.2005.07.007

Cited by 103 publications

(52 citation statements)

References 20 publications

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“…Alarmingly, the lower BPA concentration used in this study (50 mg/kg) falls in the expected human exposure range, as microgram quantities of BPA were detected in urinary samples of a reference human population (Calafat et al 2005) and in early pregnancy amniotic fluid (Ikezuki et al 2002, Engel et al 2006. This is of particular concern to fetus health, where subtle alterations will probably remain undiscovered until the onset of sexual maturity.…”

Section: Discussionmentioning

confidence: 81%

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Monje¹,

Varayoud²,

Luque³

et al. 2007

Journal of Endocrinology

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The xenoestrogen bisphenol A (BPA) is commonly ingested by humans. We examined the effects of neonatal exposure to low versus high doses of BPA over the control of estrogen receptor a (ERa) expression in the preoptic area (POA) of prepubertal female rats. Pups received s.c. injections every 48 h of BPA (high dose, 20 mg/kg and low dose, 0 . 05 mg/kg) or diethylstilbestrol (DES, 0 . 02 mg/kg) from postnatal day (PND) 1 to PND7 and were killed at PND8 or PND21. Relative expression of ERa transcripts containing alternative 5 0 -untranslated regions OS, ON, O, OT, and E1 in POA were evaluated by RT-PCR. Methylation status of ERa promoters was determined by bisulfited DNA restriction analysis and ERa protein by immunohistochemistry. In PND8, the high dose of BPA and DES diminished total ERa mRNA levels, mediated by the decreased expression of ERa-O and ERa-OT variants. In contrast, the low dose of BPA augmented total ERa mRNA by increasing the expression of the ERa-E1 variant. In PND21, both BPA doses increased total ERa mRNA by means of the augmented expression of ERa-O and ERa-OT variants. In PND21, the methylation status of the ERa promoters and the circulating levels of estradiol were similar in all experimental groups. At PND8 and PND21, DES and the high dose of BPA decreased, while the low dose of BPA increased ERa protein in the POA. These findings show that neonatal BPA exposure alters the abundance of hypothalamic ERa transcript variants and protein in a dose-dependent manner.

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Section: Discussionmentioning

confidence: 81%

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Monje¹,

Varayoud²,

Luque³

et al. 2007

Journal of Endocrinology

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“…This study suggests that BPA is transplacentally transferred to the embryo/fetal compartment. Additional studies support the idea that the fetus is continuously exposed to BPA; three studies have demonstrated that it can be measured in amniotic fluid (Engel et al 2006;Ikezuki et al 2002;Yamada et al 2002). Ikezuki et al (2002) found eight times higher concentrations of unconjugated BPA in amniotic fluid from early pregnancy compared with later pregnancy; they proposed that BPA may accumulate in early fetuses because of a lower metabolic clearance of BPA or may be conjugated more efficiently in the fetal liver during later gestation.…”

Section: Healthymentioning

confidence: 91%

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Vandenberg

Chahoud

Heindel³

et al. 2012

Ciênc. saúde coletiva

333

331

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Estudos de biomonitoração do sistema urinário, circulatório e tecidos indicam grande exposição ao Bisfenol A Resumo Bisfenol A (BPA) é um dos produtos quí-micos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinéti-ca do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco. Palavras-chave Disruptor endócrino, Exposição humana, Modelo PBPK/PBTK, Gravidez, Avaliação de risco, Toxicocinética Abstract Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.

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“…Human urinary profiles were reported at B33-70% bisphenol A glucuronide, B10-33% parent compound, and B5-34% bisphenol A sulfate conjugate (Kim et al, 2003b;Ye et al, 2005). The presence of bisphenol A in human fetal tissues or fluids demonstrates that bisphenol A is distributed to the human conceptus (Ikezuki et al, 2002;Schö nfelder et al, 2002b;Yamada et al, 2002;Kuroda et al, 2003;Engel et al, 2006) (Table 61). Results from a limited number of studies indicated that fetal bisphenol A concentrations are within the same order of magnitude as maternal blood concentrations (Schö nfelder et al, 2002b;Kuroda et al, 2003) and amniotic fluid bisphenol A concentrations are B1 order of magnitude lower than maternal blood concentrations .…”

Section: Summary Of General Toxicology and Biologicmentioning

confidence: 99%

“…Detailed descriptions of those studies are also presented below. Engel et al (2006) reported concentrations of bisphenol A in human amniotic fluid. Twenty-one samples were obtained during amniocentesis conducted before 20 weeks gestation in women who were referred to a U.S. medical center for advanced maternal age.…”

Section: Fcpsa (2005)mentioning

confidence: 99%

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

Chapin

Adams

Boekelheide

et al. 2008

Birth Defects Research Pt B

404

304

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Xenobiotic phenols in early pregnancy amniotic fluid

Cited by 103 publications

References 20 publications

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

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